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The present invention relates to methods and computer programs for rapidly screening and characterizing materials by the analysis of data acquired from images.
In combinatorial chemistry, a large number of candidate materials are created from a relatively small set of precursors and subsequently evaluated for suitability for a particular application. As currently practiced, combinatorial chemistry permits scientists to systematically explore the influence of structural variations in candidates by dramatically accelerating the rates at which they are created and evaluated. Compared to traditional discovery methods, combinatorial methods sharply reduce the costs associated with preparing and screening each candidate.
Combinatorial chemistry has revolutionized the process of drug discovery. One can view drug discovery as a two-step process: acquiring candidate compounds through laboratory synthesis or through natural products collection, followed by evaluation or screening for efficacy. Pharmaceutical researchers have long used high-throughput screening (HTS) protocols to rapidly evaluate the therapeutic value of natural products and libraries of compounds synthesized and cataloged over many years. However, compared to HTS protocols, chemical synthesis has historically been a slow, arduous process. With the advent of combinatorial methods, scientists can now create large libraries of organic molecules at a pace on par with HTS protocols.
Recently, combinatorial approaches have been used for discovery programs unrelated to drugs. For example, some researchers have recognized that combinatorial strategies also offer promise for the discovery of inorganic compounds such as high-temperature superconductors, magneto resistive materials, luminescent materials, and catalytic materials. See, for example, U.S. Pat. No. 5,776,359 and co-pending U.S. patent application No. 08/898,715 xe2x80x9cCombinatorial Synthesis and Analysis of Organometallic Compounds and Catalystsxe2x80x9d (published as WO 98/03251), which are both incorporated herein by reference.
The invention provides computer programs and computer-implemented methods for extracting and analyzing combinatorial chemical data from images.
In general, in one aspect, the invention features a computer program for evaluating a combinatorial library including a plurality of members. The program includes instructions to receive a stream of data including a series of images of the combinatorial library; to identify a plurality of regions of interest, each region corresponding to a location in each of the series of images and to a location in the combinatorial library; to determine a series of values for one or more regions of interest, the series of values for each of the one or more regions including a value for each of the images; and to calculate from each series of values for the one or more regions a figure of merit for the library member at the corresponding library location.
Implementations of the invention can include one or more of the following advantageous features. Each region of interest corresponds to a plurality of pixels in each image and the series of values for a region of interest comprises an average value for each of the corresponding plurality of pixels in each of the images. The stream of data comprises a series of images generated at a frequency of greater than about 1 frame per second. The stream of data comprises a series of images generated at a frequency of greater than about 6 frames per second. The stream of data comprises a series of images generated at a frequency of greater than about 12 frames per second. The stream of data comprises a series of images generated at a frequency of greater than about 20 frames per second. The program further includes instructions to display a graphical representation of the figures of merit. The graphical representation includes a histogram. The series of images is captured from a beginning of a combinatorial experiment to an end of the combinatorial experiment and the plurality of regions of interest may be identified after the series of images have been captured or after one or more images in the series of images has been captured. The series of images includes a series of infrared images. The figure of merit comprises an emittance change for a library member. The figure of merit comprises a phase transition point for a library member. The figure of merit comprises a thermoelectric figure of merit for a library member. The instructions to identify a plurality of regions of interest comprise instructions to receive a first user input identifying one or more regions of interest, each region having a user-defined shape. The program further includes instructions to receive a second user input defining a computation for determining a series of values for each of the one or more regions of interest. The instructions to determine a series of values for each of the one or more regions of interest include instructions to compute each value in each series in accordance with the second user input. The computation is an average for a group of pixels corresponding to a region of interest.
In general, in another aspect, the invention features a computer program on a computer-readable medium for evaluating a combinatorial library including a plurality of members. The program includes instructions to receive a stream of data including a series of images of the combinatorial library; to receive a first user input identifying one or more regions of interest, each region having a user-defined shape and each region corresponding to a location in each of the series of images and to a location in the combinatorial library; to receive a second user input defining a computation for determining a series of values for each of the one or more regions of interest, each series of values including a value for each of the images; and to determine a series of values for each of the one or more regions of interest, each value in each series being computed in accordance with the second user input.
Implementations of the invention can include one or more of the following advantageous features. The program further includes instructions to calculate from each series of values for the one or more regions a figure of merit for the library member at the corresponding library location.
In general, in another aspect, the invention features a computer program for evaluating a combinatorial chemical experiment. The program includes instructions to receive a series of images of a combinatorial library, the library including a plurality of members, the series of images captured from a beginning of the experiment to an end of the experiment; to identify, after the series of images has been captured, a plurality of regions of interest, each region corresponding to a location in each of the series of images and to a location in the combinatorial library; and to determine a series of values for one or more regions of interest, the series of values for each of the one or more regions including a value for each of the images.
In general, in another aspect, the invention features a method for evaluating a combinatorial library including a plurality of members. The method includes receiving a stream of data including a series of images of the combinatorial library; identifying a plurality of regions of interest, each region corresponding to a location in each of the series of images and to a location in the combinatorial library; determining a series of values for one or more regions of interest, the series of values for each of the one or more regions including a value for each of the images; and calculating from each series of values for the one or more regions a figure of merit for the library member at the corresponding library location.
In general, in another aspect, the invention features a computer-implemented method for evaluating a combinatorial chemical experiment. The method includes capturing a series of images of a combinatorial library, the library including a plurality of members, the series of images being captured from a beginning of the experiment to an end of the experiment and storing the series of images in memory; after the series of images has been captured, identifying a plurality of regions of interest, each region corresponding to a location in each of the series of images and to a location in the combinatorial library; and determining a series of values for one or more regions of interest, the series of values for each of the one or more regions including a value for each of the images.
In general, in one aspect, the invention features a system for evaluating a combinatorial library including a plurality of members. The system includes means for receiving a stream of data comprising a series of images of the combinatorial library; means for identifying a plurality of regions of interest, each region corresponding to a location in each of the series of images and to a location in the combinatorial library; means for determining a series of values for one or more regions of interest, the series of values for each of the one or more regions comprising a value for each of the images; and means for calculating from each series of values for the one or more regions a figure of merit for the library member at the corresponding library location.
In general, in other aspect, the invention features a system for evaluating a combinatorial library, the library including a plurality of members. The system includes means for receiving a stream of data comprising a series of images of the combinatorial library; means for receiving a first user input identifying one or more regions of interest, each region having a user-defined shape and each region corresponding to a location in each of the series of images and to a location in the combinatorial library; means for receiving a second user input defining a computation for determining a series of values for each of the one or more regions of interest, each series of values comprising a value for each of the images; and means for determining a series of values for each of the one or more regions of interest, each value in each series being computed in accordance with the second user input.
In general, in other aspect, the invention features a system for evaluating a combinatorial chemical experiment. The system includes means for receiving a series of images of a combinatorial library, the library including a plurality of members, the series of images captured from a beginning of the experiment to an end of the experiment; means for identifying a plurality of regions of interest after the series of images has been captured, each region corresponding to a location in each of the series of images and to a location in the combinatorial library; and means for determining a series of values for one or more regions of interest, the series of values for each of the one or more regions comprising a value for each of the images.
Advantages that can be seen in implementations of the invention include one or more of the following. The use of a video image sequence allows the automated extraction of data from one or more regions in every frame of the image set. This results in a time-resolved profile of the reaction of transformation being observed, rather than merely snapshots based on a limited number of selected images or image frames. Regions of interest in each image can be defined after the image sequence is captured. Calculations and corrections can be applied automatically to every region in every frame of the image set. One or more figures of merit can be extracted from some or all of the data set for each region and can be graphically displayed.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features and advantages of the invention will become apparent from the description, the drawings, and the claims.